Celiac Disease Autoimmunity

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I first came across the term “celiac disease autoimmunity” a few weeks ago as I read summaries of the article “Risk of Pediatric Celiac Disease According to HLA Haplotype and Country” that was published in the July 3[size=2], [/size]2014 issue of the [i]New England Journal of Medicine[/i](NEJM).[/font][/color][color=rgb(68,68,68)][font='Open Sans']
Based on my reading and interpretation of the article, it seems that celiac disease autoimmunity is interchangeable with the more commonly used term “potential celiac disease.” Both are used to describe cases in which people have abnormally high levels of celiac antibodies (TTG IgA) in their blood but their small intestinal biopsies do not show changes consistent with celiac disease. In other words, there is an autoimmune response to gluten that has yet to cause destruction to the villi of the small intestine. For the sake of this study, the subjects had to have abnormally high TTG IgA levels on 2 separate occasions, at least 3 months apart, to be labeled as having celiac disease autoimmunity.[/font][/color][color=rgb(68,68,68)][font='Open Sans']
The results published in NEJM come from the multinational TEDDY study, which is prospectively following a large cohort of children who are at genetically at risk of developing Type 1 (juvenile) diabetes mellitus. Since some children with both Type 1 diabetes and celiac disease share the same “at-risk” genes, HLA-DQ2 and DQ8, the researchers have also been able to follow a large group of genetically-susceptible children for the development of celiac disease. The study is ongoing and subjects are being followed for the development of both diabetes and celiac disease from infancy until age 15. This is one of many papers that have already come from the TEDDY study.[/font][/color][color=rgb(68,68,68)][font='Open Sans']
Thus far, 6403 study subjects have been found to have genes that predispose to celiac disease. Subjects have been placed into 4 risk groups:[/font][/color][color=rgb(68,68,68)][font='Open Sans']
-HLA DQ2/HLA DQ2 (homozygous for DQ2)[/font][/color][color=rgb(68,68,68)][font='Open Sans']
-HLA DQ2/HLA DQ8[/font][/color][color=rgb(68,68,68)][font='Open Sans']
-HLA DQ8/HLA DQ8 (homozygous for DQ8)[/font][/color][color=rgb(68,68,68)][font='Open Sans']
-HLA DQ8/HLA DQ4[/font][/color][color=rgb(68,68,68)][font='Open Sans']
As you can see, the first 3 groups of kids all have 2 copies of celiac-risk genes, and the 4[size=2]th[/size]group has only one copy of DQ8, so only one gene associated with celiac disease. Subjects’ testing for celiac disease autoimmunity started at age 24 months and has been repeated every year. In all, 786 of the 6403 (11%) at risk subjects were found to have celiac disease autoimmunity (elevated blood TTG IgA antibodies at least twice) at time of data analysis Overall, 25% of the children with celiac disease autoimmunity had a diagnosis of celiac disease by age 3.[/font][/color][color=rgb(68,68,68)][font='Open Sans']
The researchers broke down the risk of both celiac disease autoimmunity and celiac disease by genes and found the following risks by age 5:[/font][/color][color=rgb(68,68,68)][font='Open Sans']
[color=rgb(51,102,255)][b]Celiac Disease Autoimmunity Risk in Children with Celiac Genes by Age 5[/b][/color]:[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ2/HLA DQ2 (homozygous for DQ2): 26%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ2/HLA DQ8: 11%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ8/HLA DQ8 (homozygous for DQ8): 8%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ8/HLA DQ4: 3%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
[color=rgb(51,102,255)][b]Celiac Disease Risk in Children with Celiac Genes by Age 5[/b]:[/color][/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ2/HLA DQ2 (homozygous for DQ2): 11%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ2/HLA DQ8: 3%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ8/HLA DQ8 (homozygous for DQ8): 3%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
HLA DQ8/HLA DQ4: less than 1%[/font][/color][color=rgb(68,68,68)][font='Open Sans']
Children with both celiac disease and celiac disease autoimmunity were found to be at a higher risk of having diabetes than the general population (1% for celiac disease autoimmunity and 2% for celiac disease v. 0.3% risk for general U.S. population).[/font][/color][color=rgb(68,68,68)][font='Open Sans']
In summary, in this large study, [b]over 25% of children with the DQ2/DQ2 genotype were found to have celiac disease autoimmunity by age 5 and greater than 10% with DQ2/DQ2 were diagnosed with celiac disease by age 5.[/b] Over half of these children had no symptoms of celiac disease, therefore, there is a good chance that many of these diagnoses would have been missed if these children had not been subjects in this study.[/font][/color][color=rgb(68,68,68)][font='Open Sans']
After reading this article I am a much stronger proponent of genetic testing of children at risk for celiac disease, if possible. And, as my husband and I both carry genes associated with celiac disease, I feel much less guilty for making my own kids get screened for celiac disease, via TTG IgA blood testing, every 2 years. Lastly, I feel much more at peace for making my at-risk youngest go through having an endoscopy and small bowel biopsy earlier this summer. The statistics from this study are definitely eye-opening.[/font][/color][color=rgb(68,68,68)][font='Open Sans']
[b]Reference:[/b] Liu E, Lee HS, Aronsson CA, et al. TEDDY Study Group. [url="http://www.ncbi.nlm.nih.gov/pubmed/24988556"]Risk of pediatric celiac disease according to HLA haplotype and country.[/url] [i]N Engl J Med[/i][i].[/i] 2014 Jul 3;371(1):42-9.[/font][/color][color=rgb(68,68,68)][font='Open Sans']
Also, if you are a research geek like I am, here are some other interesting findings from the TEDDY study thus far (found via a Pubmed.gov search):[/font][/color][list]
[*]The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children.
[*]Between 15% and 20% of the infants in the study were introduced to solid foods before the age of 4 months.
[*]The median age of early-onset diabetes is at 2.3 years. 33% of the subjects with an early diagnosis of diabetes had no symptoms of diabetes.
[*]Findings have not supported the presence of viremia (recent viral infection) around the time of seroconversion in young children with rapid-onset type 1 diabetes.
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Celiac.com was founded in 1995 by Scott Adams, author of Cereal Killers, founder and publisher of Journal of Gluten Sensitivity, and founder of The Gluten-Free Mall, who had a single goal for the site: To help as many people as possible with celiac disease get diagnosed and living a happy, healthy gluten-free life!